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ESEEM analysis of multi-histidine Cu(II)-coordination in model complexes, peptides, and amyloid-β.

Silva KI, Michael BC, Geib SJ, Saxena S - J Phys Chem B (2014)

Bottom Line: We confirm that component II only contains single histidine coordination, using ESEEM and set of model complexes.The ESEEM experiments carried out on systematically (15)N-labeled peptides reveal that, in component II, His 13 and His 14 are more favored as equatorial ligands compared to His 6.Revealing molecular level details of subcomponents in metal ion coordination is critical in understanding the role of metal ions in Alzheimer's disease etiology.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry, University of Pittsburgh , Pittsburgh, Pennsylvania 15260, United States.

ABSTRACT
We validate the use of ESEEM to predict the number of (14)N nuclei coupled to a Cu(II) ion by the use of model complexes and two small peptides with well-known Cu(II) coordination. We apply this method to gain new insight into less explored aspects of Cu(II) coordination in amyloid-β (Aβ). Aβ has two coordination modes of Cu(II) at physiological pH. A controversy has existed regarding the number of histidine residues coordinated to the Cu(II) ion in component II, which is dominant at high pH (∼8.7) values. Importantly, with an excess amount of Zn(II) ions, as is the case in brain tissues affected by Alzheimer's disease, component II becomes the dominant coordination mode, as Zn(II) selectively substitutes component I bound to Cu(II). We confirm that component II only contains single histidine coordination, using ESEEM and set of model complexes. The ESEEM experiments carried out on systematically (15)N-labeled peptides reveal that, in component II, His 13 and His 14 are more favored as equatorial ligands compared to His 6. Revealing molecular level details of subcomponents in metal ion coordination is critical in understanding the role of metal ions in Alzheimer's disease etiology.

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Experimentally obtainedthree-pulse ESEEM spectra of the modelcomplexes at the maximum g⊥ position.Appearance of a peak around 9 MHz in two- and four-imidazole complexesis indicative of multiple imidazole coordination.
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fig3: Experimentally obtainedthree-pulse ESEEM spectra of the modelcomplexes at the maximum g⊥ position.Appearance of a peak around 9 MHz in two- and four-imidazole complexesis indicative of multiple imidazole coordination.

Mentions: Then the ESEEM experiments wereperformed on model complexes. TheESEEM spectra of these complexes are shown in Figure 3. Nuclear quadrupole interactions (NQI) of 14Ngive rise to features below 2 MHz. The broad feature around 4 MHzis due to the double quantum (DQ) transition of the remote nitrogenin an imidazole ring.57,58 The intensity of the DQ peakincreases with the number of imidazole rings coordinated to the Cu(II)center.48 A peak around 9 MHz (black arrowin Figure 3) is also indicative of multipleimidazole coordination.48,60 This peak is clearlyobserved in the two- and four-imidazole complexes.


ESEEM analysis of multi-histidine Cu(II)-coordination in model complexes, peptides, and amyloid-β.

Silva KI, Michael BC, Geib SJ, Saxena S - J Phys Chem B (2014)

Experimentally obtainedthree-pulse ESEEM spectra of the modelcomplexes at the maximum g⊥ position.Appearance of a peak around 9 MHz in two- and four-imidazole complexesis indicative of multiple imidazole coordination.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4120975&req=5

fig3: Experimentally obtainedthree-pulse ESEEM spectra of the modelcomplexes at the maximum g⊥ position.Appearance of a peak around 9 MHz in two- and four-imidazole complexesis indicative of multiple imidazole coordination.
Mentions: Then the ESEEM experiments wereperformed on model complexes. TheESEEM spectra of these complexes are shown in Figure 3. Nuclear quadrupole interactions (NQI) of 14Ngive rise to features below 2 MHz. The broad feature around 4 MHzis due to the double quantum (DQ) transition of the remote nitrogenin an imidazole ring.57,58 The intensity of the DQ peakincreases with the number of imidazole rings coordinated to the Cu(II)center.48 A peak around 9 MHz (black arrowin Figure 3) is also indicative of multipleimidazole coordination.48,60 This peak is clearlyobserved in the two- and four-imidazole complexes.

Bottom Line: We confirm that component II only contains single histidine coordination, using ESEEM and set of model complexes.The ESEEM experiments carried out on systematically (15)N-labeled peptides reveal that, in component II, His 13 and His 14 are more favored as equatorial ligands compared to His 6.Revealing molecular level details of subcomponents in metal ion coordination is critical in understanding the role of metal ions in Alzheimer's disease etiology.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry, University of Pittsburgh , Pittsburgh, Pennsylvania 15260, United States.

ABSTRACT
We validate the use of ESEEM to predict the number of (14)N nuclei coupled to a Cu(II) ion by the use of model complexes and two small peptides with well-known Cu(II) coordination. We apply this method to gain new insight into less explored aspects of Cu(II) coordination in amyloid-β (Aβ). Aβ has two coordination modes of Cu(II) at physiological pH. A controversy has existed regarding the number of histidine residues coordinated to the Cu(II) ion in component II, which is dominant at high pH (∼8.7) values. Importantly, with an excess amount of Zn(II) ions, as is the case in brain tissues affected by Alzheimer's disease, component II becomes the dominant coordination mode, as Zn(II) selectively substitutes component I bound to Cu(II). We confirm that component II only contains single histidine coordination, using ESEEM and set of model complexes. The ESEEM experiments carried out on systematically (15)N-labeled peptides reveal that, in component II, His 13 and His 14 are more favored as equatorial ligands compared to His 6. Revealing molecular level details of subcomponents in metal ion coordination is critical in understanding the role of metal ions in Alzheimer's disease etiology.

Show MeSH
Related in: MedlinePlus